The proposed research is an extension of previous studies performed by this investigator on the growth and development of sympathetic ganglia in vivo. Using a combination of extremely sensitive and specific biochemical and electron microscopic techniques, we have defined the developmental profiles of neurotransmitter-synthesizing enzymes, demonstrated the formation of synaptic connections during growth, indicated a bidirectional flow of regulatory information at the synapse during development of mouse superior cervical ganglion (SCG), and have begun to characterize the anterograde trans-synaptic message and its trophic effects. Thus, not only do pre-synaptic nerves regulate the development of post-synaptic neurons, but, conversely, post-synaptic neurons also influence the maturation of pre-synaptic fibers. The present studies will investigate this model system in greater depth to define the molecular mechanisms regulating neuronal maturation. More specifically, I hope to (a) further characterize the trans-synaptic message(s), (b) define the ontogeny of neurotransmitter enzyme induction in SCG, (c) characterize adrenergic enzyme maturation immunochemically and physicochemically, (d) further elucidate the role of the thyroid on neuronal maturation, (e) use the above findings in conjunction with surgical decentralization, 6-hydroxydopamine administration, and Nerve Growth Factor treatment to understand inter-neuronal communication and synaptic plasticity. BIBLIOGRAPHIC REFERENCES: Black, I.B. and Mytilineou, C.: Trans-synaptic regulation of the development of end organ innervation by sympathetic neurons. Brain Res. 101: 503-521, 1976. Dibner, M. and Black, I.B.: The effect of target organ removal on the development of sympathetic neurons. Brain Res. 103: 93-102, 1976.